MANAGEMENT OF SEVERE SEPSISManagement of Severe SepsisInitialResuscitation Diagnosis AntibioticTherapySourceControlFluid Therapy VasopressorsCorticosteroids Blood ProductAdministrationGlucoseControlBicarbonateTherapy
Guide to Recommendations’Strengths and SupportingEvidence1 = strong recommendation2 = weak recommendation or suggestionA = good evidence from randomized trialsB = moderate strength evidence from smallrandomized trial(s) or multiple goodobservational trialsC = weak or absent evidence, mostly drivenby consensus opinion
Initial ResuscitationProtocolized, quantitative resuscitation ofpatients with sepsis-induced tissuehypoperfusion (defined in this document ashypotension persisting after initial fluidchallenge or blood lactate concentration ≥ 4mmol/L).Goals during the first 6 hrs of resuscitation:a) CVP 8–12 mmHgb) MAP ≥ 65 mm Hgc) Urine output ≥ 0.5 mL/kg/hrd) ScvO2 70% or 65%, respectively (grade 1C).
Initial ResuscitationIn patients with elevated lactate levelstargeting resuscitation to normalizelactate (grade 2C).
Surviving Sepsis Campaign BundlesTO BE COMPLETED WITHIN 3 HOURS:1) Measure lactate level2) Obtain blood cultures prior to administration of antibiotics3) Administer broad spectrum antibiotics4) Administer 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/LTO BE COMPLETED WITHIN 6 HOURS:5) Apply vasopressors (for hypotension that does not respond to initialfluid resuscitation) to maintain a MAP ≥65 mmHg6) In the event of persistent arterial hypotension despite volumeresuscitation (septic shock) or initial lactate ≥4 mmol/L :– Measure CVP– Measure ScvO27) Remeasure lactate if initial lactate was elevated
DiagnosisCultures as clinically appropriate beforeantimicrobial therapy if no significant delay (>45 mins) in the start of antimicrobial(s) (grade1C).At least 2 sets of blood cultures (both aerobicand anaerobic bottles) be obtained beforeantimicrobial therapy with at least 1 drawnpercutaneously and 1 drawn through eachvascular access device, unless the devicewas recently (<48 hrs) inserted (grade 1C).
DiagnosisUse of the 1,3 beta-D-glucan assay (grade2B), mannan and anti-mannan antibodyassays (2C), if available, and invasivecandidiasis is in differential diagnosis ofcause of infection.
DiagnosisImaging studies performed promptly toconfirm a potential source of infection.
Antimicrobial TherapyAdministration of effective intravenousantimicrobials within the first hour ofrecognition of septic shock (grade 1B) andsevere sepsis without septic shock (grade1C) as the goal of therapy.
Antimicrobial TherapyUse of low procalcitonin levels or similarbiomarkers to assist the clinician in thediscontinuation of empiric antibiotics inpatients who initially appeared septic, buthave no subsequent evidence of infection(grade 2C).
Antimicrobial TherapyCombination empirical therapy for neutropenicpatients with severe sepsis (grade 2B) and forpatients with difficult-to-treat, multidrug-resistantbacterial pathogens such as Acinetobacter andPseudomonas spp. (grade 2B).For patients with severe infections associated withrespiratory failure and septic shock,combination therapy with an extended spectrumbeta-lactam and either an aminoglycoside or afluoroquinolone is for P. aeruginosa bacteremia(grade 2B).A combination of beta-lactam and macrolide forpatients with septic shock from bacteremicStreptococcus pneumoniae infections (grade 2B).
Antimicrobial TherapyEmpiric combination therapy should not beadministered for more than 3–5 days.De-escalation to the most appropriate singletherapy should be performed as soon asthe susceptibility profile is known (grade2B).
Antimicrobial TherapyDuration of therapy typically 7–10 days;longer courses may be appropriate inpatients who have a slow clinical response,undrainable foci of infection, bacteremiawith S. aureus; some fungal and viralinfections or immunologic deficiencies,including neutropenia (grade 2C).
Antimicrobial TherapyAntiviral therapy initiated as early aspossible in patients with severe sepsis orseptic shock of viral origin (grade 2C).
Source ControlA specific anatomical diagnosis of infectionrequiring consideration for emergentsource control be sought and diagnosed orexcluded as rapidly as possible, andintervention be undertaken for sourcecontrol within the first 12 hr after thediagnosis is made, if feasible (grade 1C).
Source ControlWhen source control in a severely septicpatient is required, the effectiveintervention associated with the leastphysiologic insult should be used (eg,percutaneous rather than surgicaldrainage of an abscess).
Source ControlIf intravascular access devices are apossible source of severe sepsis or septicshock, they should be removed promptlyafter other vascular access has beenestablished.
Fluid TherapyCrystalloids as the initial fluid of choicein the resuscitation of severe sepsis andseptic shock (grade 1B).Against the use of hydroxyethyl starchesfor fluid resuscitation of severe sepsis andseptic shock (grade 1B).
Fluid TherapyAlbumin in the fluid resuscitation of severesepsis and septic shock when patientsrequire substantial amounts of crystalloids(grade 2C).
Fluid TherapyInitial fluid challenge in patients with sepsis-induced tissue hypoperfusion withsuspicion of hypovolemia to achieve aminimum of 30 mL/kg of crystalloids(grade 1C).
Fluid TherapyFluid challenge technique be appliedwherein fluid administration is continuedas long as there is hemodynamicimprovement either based on dynamic (eg,change in pulse pressure, stroke volumevariation) or static (eg, arterial pressure,heart rate) variables.
VasopressorsVasopressor therapy initially to target aMAP of 65 mmHg (grade 1C).Norepinephrine as the first choicevasopressor (grade 1B).
VasopressorsEpinephrine (added to and potentiallysubstituted for norepinephrine) when anadditional agent is needed to maintainadequate blood pressure (grade 2B).Vasopressin 0.03 units/minute can beadded to norepinephrine with intent ofeither raising MAP or decreasingnorepinephrine dosage.
VasopressorsDopamine as an alternative vasopressoragent to norepinephrine only in highlyselected patients (eg, patients with low riskof tachyarrhythmias and absolute orrelative bradycardia) (grade 2C).
VasopressorsA trial of dobutamine infusion up to 20mg/kg/min be administered or added tovasopressor in the presence ofa) myocardial dysfunction as suggested byelevated cardiac filling pressures and lowcardiac output, orb) ongoing signs of hypoperfusion, despiteachieving adequate intravascular volumeand adequate MAP (grade 1C).
CorticosteroidsNot using intravenous hydrocortisone totreat adult septic shock patients ifadequate fluid resuscitation andvasopressor therapy are able to restorehemodynamic stability.In case this is not achievable, we suggestintravenous hydrocortisone alone at adose of 200 mg per day (grade 2C).When hydrocortisone is given, usecontinuous flow (grade 2D).
Blood Product AdministrationOnce tissue hypoperfusion has resolved andin the absence of extenuatingcircumstances, such as myocardialischemia, severe hypoxemia, acutehemorrhage, or ischemic heart disease,we recommend that RBC transfusionoccur only when hemoglobin <7.0 g/dLto target a hemoglobin of 7.0 –9.0 g/dLin adults (grade 1B).
Blood Product AdministrationIn patients with severe sepsis, administerplatelets prophylactically when counts are<10,000/mm3 in the absence of apparentbleeding.We suggest prophylactic platelet transfusionwhen counts are < 20,000/mm3 if thepatient has a significant risk of bleeding.Higher platelet counts (≥50,000/mm3) areadvised for active bleeding, surgery, orinvasive procedures (grade 2D).